Malaria Resistance (Duffy Antigen)
Duffy Antigen The Duffy antigen, also known as Duffy Antigen Receptor for Chemokines (DARC), Fy glycoprotein (FY), or Cluster Differentiation 234 (CD234), is a protein that is found on the outside of red blood cells. In 1950, a hemophiliac with multiple transfusions was reported to have an anti-Fya. This was the first reported case, and the name is derived from the hemophiliac patient in which the antigen was first found. The gene that encodes this glycosylated membrane protein is found on chromosome 1. The two main forms of the antigen are Fya and Fyb, which only differ by one amino acid [1] Studies initially revealed three phenotypes, including Fy(a+b+), Fy(a+b-), and Fy (a-b+). The Fy (a-b-) phenotype is one that results fro a T to C point mutation in the erythroid specific promoter. This results in an erythrocyte silent phenotype (Howes et al., 2011). Many African Americans have the erythrocyte silent phenotype, resulting in a Fy-b silent allele. Duffy negative Caucasians are rare, about 3.5% of the population have the erythrocyte silent phenotype. Plasmodium vivax Plasmodium vivax is one of five species of protozoal parasites that causes malaria. An outline of the invasion process of this parasite is shown in the figure above. The protozoa resides within mosquitoes, and makes its way to the salivary glands. When a mosquito bites an individual, the parasite is able to enter the bloodstream. The parasite contains a Duffy binding protein, which recognizes DARC on red blood cells. This binding protein is essential for the pathogen to invade host erythrocytes. Particular residues of the Duffy binding protein of Plasmodium vivax are important for recognition of host DARC [2] . These residues are found within Duffy Binding Protein region II (DBPII). Anti-DBPII antibodies have been shown to provide protection against pathogen invasion. Clincal Implications Symptoms of malaria range from headache and fever to coma and death. Currently, there is no effective vaccine for the disease. Duffy Binding Protein has been shown to be an important component of the junction that is formed during the invasion process. This protein is therefore a desirable target for vaccine development [1] . Rapid blood tests and microscope examination are currently being used for detection methods. Malaria Resistance As described earlier, a T to C point mutation at nucleotide 46 causes the Duffy antigen to not be present on red blood cells http://www.ncbi.nlm.nih.gov/pubmed?cmd=Search&term=7663520%7C [3. Since Plasmodium vivax needs this antigen to invade the host via the Duffy Binding Protein, invasion can no longer occur under these circumstances. Individuals with and Fy(a-b-) phenotype are therefore resistant to malaria induced by Plasmodium vivax. SNP/ John Burke's Genotype Three possibilities of this SNP: CC- two copies of C in which there is no Duffy antigen on red blood cells and therefore resistance to malaria induced by Plasmodium vivax. CT- may be resistant to malaria induced by Plasmodium vivax. TT- Dr. Burke's genotype. The Duffy antigen is expressed and therefore no resistance to malaria induced by Plasmodium vivax. Dr. Burke should not have any raised concerns, however, as malaria does not manifest in the United States. According to the CDC, malaria was eliminated in the United States between the years of 1947 and 1951. References 1. Howes RE, Patil AP, Piel FB, Nyangiri OA, Kabaria CW, Gething PW, Zimmerman PA, Barnadas C, Beall CM, Gebremedhin A, Menard D, Williams TN, Weatherall DJ, Hay S. The global distribution of the Duffy blood group. Nature Commun 2013 (2): 266. 2.Ntumngia FB, Schloegel J, McHenry AM, Barnes SJ, George MT, Kennedy S, Adams JH. Immunogenicity of single versus mixed allele vaccines of Plasmodium vivax Duffy binding protein region II. Vaccine 2013 (31): 4382-4388. 3.Tournamille C, Colin Y, Cartron JP, Le Van Kim C. Disruption of the GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals. Nat Genet 1995 (2): 224-228. 4. Grimberg BT, Udomsangpetch R, Xainli J, McHenry A, Panichakul T, Sattabongkot J, Cui L, Bockarie M, Chitnis C, Adams J, Zimmerman P, King CL. Plasmodium vivax invasion od human erythrocytes inhibited by antibodies directed against the duffy binding protein. PLOS Medicine 2007 (4) 1940-1948. 5. Duffy antigen system Wiki 6. Malaria Wiki